mVASC Product Description

MVT has developed a way to stabilize the components of microvascular tissue into an off-the-shelf product that capitalizes on the powerful angiogenic properties of microvascular fragments. mVASC^® is a human microvascular tissue allograft that has been processed and lyophilized, while preserving structural tissue fragments, associated nonviable cells, and inherent biological factors that enhance healing potential by increasing blood supply, regulating the immune cell reaction, modulating inflammation, and providing the foundation for tissue repair. mVASC is terminally sterilized and room temperature stable for 5 years.

mVASC is marketed in accordance with FDA HCT/P regulations, and is restricted to homologous use for the repair, reconstruction, replacement or supplementation of microvascular tissues. It can be used wherever microvascular deficiencies exist. For example, mVASC can be added to a nonhealing wound to restore blood flow.

The composition and function of mVASC has been extensively studied. Characterization of structural and biologic factors intrinsic to mVASC shows that key angiogenic and neurotrophic factors in microvascular tissue are preserved. Recognized preclinical models, including mouse pressure ulcer and hindlimb ischemia studies demonstrated that mVASC improved healing, and increased neovascularization and blood flow, respectively.

mVASC Pre-Clinical Studies

Blood Perfusion Study
Wound Healing Study
Angiogenesis Study

Blood Perfusion Study: Hindlimb Ischemia Model

mVASC demonstrates significantly greater re-perfusion and vascular reconstruction in a recognized mouse angiogenesis model.

A hindlimb ischemia model was used to study the effect of mVASC on ischemia-reperfusion following the ligation and transection of the femoral artery in one hindlimb of 8 SCID male mice.
Either 100 μL of saline control or 100 μL of mVASC resuspended in sterile water was injected on days 0, 3 and 7 into the adductor and gastrocnemius muscles of the ischemic limb. Each injection contained 1.7x10⁵ mVASC tissue fragments. Measurement of tissue perfusion was made on days 0, 7 and 14 using Laser Doppler Imaging under anesthesia. Relative mean perfusion rate was calculated by quantifying the blood flow in the ischemic limb in relation to the non-ischemic control limb.
Representative Doppler images are shown in the figure below. Complete restriction of blood flow in the injured leg following the ligation and transection of the femoral artery was achieved.
At Day 7, some reperfusion was evident in both control and mVASC-treated mice, but by Day 14, the blood flow in the control animals had stalled and tissue necrosed. In mVASC-treated animals, the vascularization continued with nearly complete restoration of blood flow. Overall, the mean perfusion ratios at day 14 were 59 ± 4% of the contralateral control limb for the control group and 82 ± 8% of the contralateral limb for the mVASC group (p = 0.002).

Publication

Dobke M, et al. Microvascular tissue as a platform technology to modify the local microenvironment and influence the healing cascade. Regen Med, 15(2):1313 (2020).

Wound Healing: Pressure Ulcer Model

mVASC significantly increased the rate of wound healing in a recognized mouse pressure ulcer model, demonstrating its potential as an advanced treatment for restoring normal tissue function in ischemic wounds.

The ability of mVASC to accelerate wound regeneration was evaluated in a validated mouse pressure ulcer model. Two identical pressure ulcer injuries were created in 50 female C57BL/6 mice using two 24-hour cycles of skin ischemia/reperfusion.
The ulcers were either treated with topical mVASC, rehydrated mVASC injection, or saline control injection, and assessed daily for closure rates, scab formation/removal, and temperature. Treatment group cohorts were sacrificed at 3, 7, or 14 days postinjury, and ulcer explants were evaluated for inflammatory, reparative, and stem cell frequencies, as well as histology and immunofluorescence analysis.
mVASC accelerated wound closure; most notably, topical mVASC significantly increased mean closure from day 5 (13% versus ˗9%) through day 13 (92% versus 38%) compared with saline controls (p < 0.05). mVASC also expedited scab removal and raised skin temperature, consistent with increased blood flow. In addition, mVASC significantly accelerated disappearance of inflammatory cells while increasing vascular and neural cell populations upregulating expression angiogenic and tissue repair factors.

Publication

Gimble J et al. A Novel, Sterilized Microvascular Tissue Product Improves Healing in a Murine Pressure Ulcer Model. Plastic and Reconstructive Surgery – Global Open, 6(11):e2010 (2018).

Angiogenesis Study: Matrigel Ingrowth Assay

mVASC demonstrates significantly more newly formed blood vessels and more mature (larger diameter) vessels in a recognized angiogenesis model.

An established severe combined immunodeficiency (SCID) mouse Matrigel model was used to study blood vessel ingrowth, comparing two doses of mVASC versus saline control.
The Matrigel plugs were implanted subcutaneously into the right and left dorsal flanks of each mouse. After 2 weeks, the plugs were excised, fixed and stained with antibodies against surface markers for endothelial cells, and analyzed for vessel formation using immunofluorescent imaging.
The newly formed vessels were quantified and categorized into three groups: (1) small tubes with a diameter of <10 μm without a visible lumen; (2) medium tubes with a visible lumen and (3) large tubes with a diameter of more than 10 μm with a visible lumen and visible erythrocytes in the lumen.
Per the graph below, blood vessel ingrowth for the low and high concentrations of mVASC fragments increased 33% and 139% over the control, respectively. mVASC also led to more mature vessels, as quantified by the greater number of larger diameter vessels, predominantly due to the increase in medium-sized vessels.

Publication

Dobke M, et al. Microvascular tissue as a platform technology to modify the local microenvironment and influence the healing cascade. Regen Med, 15(2):1313 (2020).

mVASC Clinical Applications

Advanced Woundcare

Vascular Deficiencies in DFUs
mVASC Clinical Evidence in DFUs

Vascular Deficiencies in Diabetic Foot Ulcers (DFUs)

Nonhealing diabetic foot ulcers (DFUs) are stalled wounds with compromised repair capabilities. Less than one quarter of these ulcers will heal with standard wound care after 12 weeks. ¹

34%

of the 34 million diabetics in the US

will develop a DFU during their lifetime

>45%

5-year mortality after amputation from a DFU

The large clinical and economic burden of nonhealing DFUs continues to escalate, and includes multiple admissions, treatment for infection, neuropathy, and amputations. Up to 34% of the 34 million diabetics in the US will develop a DFU during their lifetime.^2,3 Despite use of advanced therapeutics, the 5-year mortality after amputation from a diabetic foot ulcer is over 45%.⁴

In addition to addressing the compromised vasculature contributing to a nonhealing DFU, microvascular tissue also has the potential to impact the loss of sensation common in diabeties. Leaky capillary walls in diabetic tissue decrease blood flow to the surrounding microvascular tissues, resulting in structural changes that also damage the nerves, and ultimately leading to neuropathy associated with the occurrence and recurrence of DFUs. ^5,6

A functioning microvasculature is crucial for closing nonhealing wounds and re-establishing a normal environment that translates into well-perfused, sensate, high quality tissue.

References:

¹Margolis D, et al. Diabetes Care. 22:692 (1999). (25% healed at 12w)

²Armstrong DG, et al. N Engl J Med. 376:24 (June 2017). (up to 34% of 34M)

³National Diabetes Statistics Report, 2020. (up to 34% of 34M)

⁴Armstrong DG, et al. J Foot Ankle Res. 13:16 (2020). (5y mortality <45%)

⁵Thrainsdottir S, et al. Diabetes. 52:2615 (2003). (vascular changes lead to neuropathy)

⁶Lavery L, et al. Arch. Intern. Med. 158:157 (1998). (neuropathy predictor of DFU)

HIFLO Clinical Trial

MVT recently completed the HIFLO trial (HEALING IN DIABETIC FOOT ULCERS WITH MICROVASCULAR TISSUE). The HIFLO trial is a multi-center Level 1 prospective 100-patient randomized controlled trial of allogeneic microvascular tissue (mVASC) in nonhealing neuropathic diabetic foot ulcers.

The HIFLO trial represents a new bar for evaluating advanced wound products. The study utilized four predefined criteria and an independent blinded panel of three adjudicators to determine closure, included a real-world patient population of Wagner 1 and 2 DFUs (uncommon in a large RCT), and is the first large RCT to include sub studies involving perfusion and peripheral neuropathy.

mVASC is unique among advanced wound therapies, as it represents a ‘biological matching’ of the solution to a disease state. The HIFLO trial represents the first demonstration of using microvascular elements to treat microvascular dysfunction in a randomized study. By leveraging intrinsic healing mechanisms, mVASC achieved superior wound closure and quality of healing, including a marked improvement in wound regional blood flow and significant increases in local and regional sensation.

Overall, mVASC increased the odds of healing by 9 times over standard of care treatment. The higher percentage of closed ulcers and faster time to healing with mVASC may mitigate some of the risk factors associated with DFU complications, such as infection, reoccurrence and amputation. The improvements in blood flow and neuropathy may also mitigate these risk factors, though additional studies should be performed.

mVASC Product Description